Methylation of Ylidene-Triazenes: Insight and Guidance for 1,3-Dipolar Cycloaddition Reactions

被引:19
作者
Tennyson, Andrew G. [1 ]
Moorhead, Eric J. [1 ]
Madison, Brian L. [1 ]
Er, Joyce A. V. [1 ]
Lynch, Vincent M. [1 ]
Bielawski, Christopher W. [1 ]
机构
[1] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA
基金
美国国家科学基金会;
关键词
Nitrogen heterocycles; Dipolar cycloaddition; Click chemistry; N-Heterocyclic carbenes; Azides; Triazenes; ANTITUMOR AGENT; CRYSTAL-STRUCTURE; X-RAY; POLYMER; AZIDES; CHEMISTRY; LIGATION; DELIVERY; ALKYNES; ROUTES;
D O I
10.1002/ejoc.201000939
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Reaction of 1,3-dimesitylimidazolylidene (1) with p-functionalized phenyl azides 2 (a: H, b: OCH3, c: NO2) afforded the respective imidazolylidene-triazenes 3 in good yields (65-99 %). Subsequent treatment with methyl iodide produced the corresponding methylated products 4 in near-quantitative yields (99 %). Analysis by NOESY 1D NMR spectroscopy and single-crystal X-ray diffraction revealed that the methylation reaction was regioselective and occurred at the nitrogen atom most distal from the heterocycle. Consistent with the formation of ionic salts, the H-1 NMR signals for the imidazole protons in 4 were shifted > 0.5 ppm downfield compared to 1, indicating the accumulation of positive charge. Similarly, the lambda(max) values recorded for 4 exhibited a much narrower range than those for 3 (16 vs. 77 nm, respectively), suggesting that the frontier orbital energies within the former were dominated by Coulombic effects (i.e., the acquisition of positive charge) as opposed to electronic effects from the electron-donating or withdrawing groups of the aryl azide. Whereas computational analyses revealed that the observed regioselectivity of the methylation reaction may be explained by thermodynamics, kinetic factors (e.g., sterics) may also be important contributors and render one reaction pathway significantly more accessible due to a lower activation energy.
引用
收藏
页码:6277 / 6282
页数:6
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